The overall objective of this research is to define the mechanisms, kinetics and products of biotransformation of volatile halogenated anesthetic drugs and the factors affecting metabolism of these drugs in man, so as to obtain some insight into the causes of the rare toxic reactions which follow general anesthesia. Immediate goals are to determine the quantities and time course of excretion of fluoride ion and organic fluorine compounds in urine of volunteer surgical patients following exposure to isoflurane and two halogenated cyclobutanes, Compounds 42M-9 and 22M-13, and to identify the urinary organic metabolites of these drugs. We plan to continue studies of the roles of factors such as age, sex, prior drug exposure and preexisting disease on biotransformation, and to investigate the fate of the products of biotransformation including long-term retention in tissues and occurrence in the fetus. We will continue to study the mechanism of impairment of urine concentrating ability followng methoxyflurane anesthesia.